Recent reports support the hypothesis that a mechanism by which anthracyclines cause cardiotoxicity involves the formation of drug free radical and enhanced orxyradical production. It is possible that at least a portion of the antitumor activity of anthracyclines may also result from anthracycline-mediated oxyradical production leading to damage to intracellular membranes through the process of lipid peroxidation. Information relevant to this possibility is presently lacking, and, therefore, this project was designed to evaluate the oxyradical hypothesis of cytotoxicity with isolated microsomal and mitochondria subcellular fractions from several model tumors.